Ca(2+) influx through nonselective cation channels plays an essential role in endothelin-1-induced mitogenesis in C6 glioma cells.
Neuropharmacology
; 41(3): 331-40, 2001 Sep.
Article
en En
| MEDLINE
| ID: mdl-11522324
ABSTRACT
Ca(2+) channels activated by endothelin-1 (ET-1) in C6 glioma cells (C6 cells) were characterized using whole-cell patch-clamps and by monitoring the intracellular free Ca(2+) concentration ([Ca(2+)](i)), when administering Ca(2+) channel blockers such as LOE 908 and SK&F 96365. Using this methodology, the Ca(2+) channels involved in ET-1-induced mitogenesis were identified. The patch-clamp study and [Ca(2+)](i) monitoring showed that 10 nM ET-1 activated two types of Ca(2+)-permeable nonselective cation channels (NSCC); one was sensitive to LOE 908 but resistant to SK&F 96365 (NSCC-1) and the other was sensitive to both LOE 908 and SK&F 96365 (NSCC-2). Conversely, 0.1 nM ET-1 activated only NSCC-1.ET-1-induced mitogenesis in a concentration-dependent manner, with the maximum effect arising at concentrations > or =10 nM. LOE 908 completely suppressed the 10 nM ET-1-induced mitogenesis, whereas SK&F 96365 only partially suppressed it. The IC(50) values of these blockers for the ET-1-induced mitogenesis were similar to those for the 10 nM ET-1-induced increase in [Ca(2+)](i). In contrast, LOE 908 completely suppressed 0.1 nM ET-1-induced mitogenesis, whereas SK&F 96365 did not affect it.Collectively, these results demonstrate that the sustained increase in [Ca(2+)](i), via NSCC-1 and NSCC-2, may be essential for ET-1-induced mitogenesis in C6 cells. Moreover, the sensitivity of NSCC-1 to ET-1 is higher than that of NSCC-2 to ET-1.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Encefálicas
/
Calcio
/
Endotelina-1
/
Glioma
/
Canales Iónicos
/
Mitosis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neuropharmacology
Año:
2001
Tipo del documento:
Article
País de afiliación:
Japón